AJM Theme Issue: GI and NutritionReviewSelective Serotonin Reuptake Inhibitors and Risk of Upper GI Bleeding: Confusion or Confounding?
Section snippets
Methods
MEDLINE, EMBASE, the Cochrane Controlled Trials register, and the Food and Drug Administration (FDA) website were searched for studies addressing SSRI use and UGIB in humans from 1980 to May 2005, and the literature was systematically reviewed.
Keywords used were “SSRI(s)” or “selective serotonin reuptake inhibitor (s)” and “bleeding” or “hemorrhage”; different commonly used brand names of SSRIs including fluoxetine (Prozac, Eli Lilly and Company, Indianapolis, IN), sertraline (Zoloft [Pfizer
Selective Serotonin Reuptake Inhibitors and Upper Gastrointestinal Bleeding
Published clinical evidence on the relationship between SSRI use and GI bleeding is limited to observational studies without any clinical trials. Thirty-eight articles including case reports and reviews related to SSRI use and bleeding were initially identified and retrieved. Only 6 articles (4 cohort and 2 case-control studies) that addressed GI bleeding met inclusion criteria.14, 20, 21, 22, 23, 24 Two of them were in letter format20 or abstract form.24 One cohort study, which concluded no
Mechanisms of Selective Serotonin Reuptake Inhibitors Increase Bleeding Risk
The concentration of serotonin (5-HT) in platelets is critical for maintaining platelet hemostatic function; serotonin released from the platelet potentiates platelet aggregation induced by adenosine diphosphate or thrombin.29 In principle, SSRIs can impair hemostatic function because serotonin is not synthesized in platelets but taken up from the circulation by serotonin transporters on the platelets.30 SSRIs at therapeutic doses block this reuptake of serotonin by platelets leading to a
Conclusions
Only a few epidemiology studies have investigated the association between SSRIs and UGIB. They provide weak evidence to support a link between SSRIs and UGIB at a population level. SSRIs may precipitate GI bleeding in certain circumstances, such as in those with a preexisting hemostatic defect or who are taking concomitant drugs that cause GI injury. Available evidence shows that concurrent use of NSAIDs or low-dose aspirin with SSRIs greatly increases the risk of UGIB. It is important to
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